Li Jian-Hua, Shi Xian-Zhe, Lv Shen, Liu Min, Xu Guo-Wang
Laboratory Center of Molecular Biology, the Second Hospital of Dalian Medical University, Dalian 116027, Liaoning Province, China.
World J Gastroenterol. 2005 Jul 28;11(28):4363-6. doi: 10.3748/wjg.v11.i28.4363.
To investigate the relationship between Helicobacter pylori (H pylori) infection, microsatellite instability and the expressions of the p53 in gastritis, intestinal metaplasia and gastric adenocarcinoma and to elucidate the mechanism of gastric carcinogenesis relating to H pylori infection.
One hundred and eight endoscopic biopsies and gastric adenocarcinoma were available for the study including 33 cases of normal, 45 cases of gastritis, 30 cases of intestinal metaplasia, and 46 cases of gastric adenocarcinoma. Peripheral blood samples of these patients were also collected. H pylori infection and p53 expressions were detected by means of streptavidin-peroxidase (SP) immunohistochemical method. Microsatellite loci were studied by PCR-SSCP-CE using the markers BAT-26, D17S261, D3S1283, D2S123, and D3S1611. MSI was defined as the peak shift in the DNA of the gastric tissue compared with that of the peripheral blood samples. Based on the number of mutated MSI markers, specimens were characterized as high MSI (MSI-H) if they manifested instability at two or more markers, low MSI (MSI-L) if unstable at only one marker, and microsatellite stable (MSS) if they showed no instability at any marker.
H pylori infection was detected in the samples of gastritis, intestinal metaplasia, and gastric adenocarcinoma and the infection frequencies were 84.4%, 76.7%, and 65.2%, respectively, whereas no H pylori infection was detected in the samples of normal control. There was a significant difference in the infection rates between gastritis and carcinoma samples (P = 0.035). No MSI was detected in gastritis samples, one MSI-H and two MSI-L were detected among the 30 intestinal metaplasia samples, and 12 MSI-H and 3 MSI-L were detected in the 46 gastric carcinomas. In those gastric carcinomas, the MSI-H frequency in H pylori-positive group was significantly higher than that in H pylori-negative group. No p53 expression was detected in the normal and gastritis samples from dyspeptic patients. P53-positive immunohistochemical staining was detected in 13.3% of intestinal metaplasia samples and in 43.5% of gastric carcinoma samples. The levels of p53 in H pylori-positive samples were higher than those in the negative group when the carcinoma samples were subdivided into H pylori-positive and -negative groups (P = 0.013). Eight samples were detected with positive p53 expression out of the 11 MSI-H carcinomas with H pylori infection and no p53 expression could be seen in the H pylori-negative samples.
H pylori affect the p53 pattern in gastric mucosa when MMR system fails to work. Mutations of the p53 gene seem to be an early event in gastric carcinogenesis.
探讨幽门螺杆菌（H pylori）感染、微卫星不稳定性及p53在胃炎、肠化生及胃腺癌中的表达之间的关系，阐明H pylori感染与胃癌发生的机制。
选取108例内镜活检及胃腺癌标本用于研究，包括33例正常组织、45例胃炎组织、30例肠化生组织及46例胃腺癌组织。同时采集这些患者的外周血样本。采用链霉亲和素-过氧化物酶（SP）免疫组化法检测H pylori感染及p53表达。应用BAT-26、D17S261、D3S1283、D2S123和D3S1611标记物，通过PCR-SSCP-CE研究微卫星位点。微卫星不稳定性（MSI）定义为胃组织DNA与外周血样本DNA相比出现峰移。根据突变的MSI标记物数量，若标本在两个或更多标记物上表现出不稳定性，则为高MSI（MSI-H）；若仅在一个标记物上不稳定，则为低MSI（MSI-L）；若在任何标记物上均未显示不稳定性，则为微卫星稳定（MSS）。
在胃炎、肠化生及胃腺癌样本中均检测到H pylori感染，感染率分别为84.4%、76.7%和65.2%，而正常对照组样本未检测到H pylori感染。胃炎和癌组织样本的感染率有显著差异（P = 0.035）。胃炎样本中未检测到MSI，30例肠化生样本中检测到1例MSI-H和2例MSI-L，46例胃癌中检测到12例MSI-H和3例MSI-L。在这些胃癌中，H pylori阳性组的MSI-H频率显著高于H pylori阴性组。消化不良患者的正常及胃炎样本中未检测到p53表达。13.3%的肠化生样本及43.5%的胃癌样本检测到p53阳性免疫组化染色。将癌组织样本分为H pylori阳性和阴性组后，H pylori阳性样本中的p53水平高于阴性组（P = 0.013）。11例伴有H pylori感染的MSI-H胃癌中有8例检测到p53表达阳性，而H pylori阴性样本中未见p53表达。
当错配修复系统功能失效时，H pylori影响胃黏膜中的p53模式。p53基因突变似乎是胃癌发生的早期事件。
